Opposing α- and β-adrenergic mechanisms mediate dose-dependent actions of noradrenaline on supraoptic vasopressin neurones in vivo

The effects of pressure-applied noradrenaline (NA) on the activity of neurosecretory cells of the supraoptic nucleus (SON) were examined in anaesthetized male rats. Spontaneously active, antidromically identified neurosecretory cells were classified as vasopressin (VP)-secreting on the basis of activity patterns and responsiveness to baroreceptor activation. The probability of encountering VP units was enhanced by confining electrode penetrations to the caudal aspect of the SON. Application of low concentrations of NA (50-150 microM) excited 75% of putative VP neurones tested (n = 45), while very high concentrations (1-100 mM) were inhibitory (79%, n tested = 14). The excitatory effects of NA were blocked by the alpha 1 antagonist prazosin (0.1-5 microM, n = 9) and mimicked by application of the alpha 1 agonist methoxamine (300 microM-1 mM, n = 29). The alpha 2 agonist clonidine (800 microM-1 mM) also frequently elicited mild excitations (92%, n tested = 13); however, this was commonly followed by an extended period of quiescence. Neither the alpha 2 antagonist yohimbine (5 microM, n = 4) nor the beta-adrenoreceptor antagonist timolol (5-20 microM, n = 6) blocked NA-induced excitations. The inhibitory effects of high concentrations of NA, however, were blocked by the application of timolol (5-20 microM, n = 5). It is suggested that the excitatory effect of low concentrations of NA on VP neurones reflects the actions of this substance when endogenously secreted at normal sites of release within the SON.